3-66251482-A-G

Position:

• chr3-66251482-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001379210.1(SLC25A26):​c.300+8170A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,124 control chromosomes in the GnomAD database, including 3,941 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (3941 hom., cov: 32)
• Consequence: SLC25A26 NM_001379210.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.60

Genes affected

SLC25A26 (HGNC:20661): (solute carrier family 25 member 26) This gene is a member of the mitochondrial carrier family which includes nuclear-encoded transporters localized on the inner mitochondrial membranes. Members of the family transport important small molecules across the mitochondrial inner membrane. This protein is involved in the transport of S-adenosylmethionine (SAM) into the mitochondria. Mutations in this gene are associated with combined oxidative phosphorylation deficiency 28. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Apr 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SLC25A26	NM_001379210.1	c.300+8170A>G		intron_variant		ENST00000354883.11	NP_001366139.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SLC25A26	ENST00000354883.11	c.300+8170A>G		intron_variant		2	NM_001379210.1	ENSP00000346955	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32888 AN: 152006 Hom.: 3931 Cov.: 32

Gnomad AFR AF: 0.123

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.278

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.118

Gnomad FIN AF: 0.352

Gnomad MID AF: 0.155

Gnomad NFE AF: 0.252

Gnomad OTH AF: 0.206

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.216 AC: 32929 AN: 152124 Hom.: 3941 Cov.: 32 AF XY: 0.220 AC XY: 16359 AN XY: 74364

Gnomad4 AFR AF: 0.123

Gnomad4 AMR AF: 0.279

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.118

Gnomad4 FIN AF: 0.352

Gnomad4 NFE AF: 0.252

Gnomad4 OTH AF: 0.203

Alfa AF: 0.241 Hom.: 1938

Bravo AF: 0.210

Asia WGS AF: 0.150 AC: 521 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.012
DANN	Benign	0.23

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs13076104; hg19: chr3-66301906;